NCI CANCERLIT^® Search: Chemotherapy for Non-small Cell Lung Cancer - September 2001

Last Modified: November 1, 2001

A three-drug regimen (gemcitabine, ifosfamide and cisplatin) for advanced non-small-cell lung cancer.
A prospective study of gemcitabine and carboplatin as first-line therapy in advanced non-small cell lung cancer: toxicity of a three- versus a four-week schedule.
Gemcitabine/carboplatin versus cisplatin/etoposide for patients with poor-prognosis small cell lung cancer: a phase III randomized trial with quality-of-life evaluation.
Gemcitabine and carboplatin for patients with advanced non-small cell lung cancer.
Recent advances in the chemotherapy of non-small cell lung cancer.
Paclitaxel in combination with carboplatin as salvage treatment in refractory small-cell lung cancer (SCLC): a multicenter phase II study.
Management of patients with advanced non-small-cell lung cancer.
Treatment of advanced non-small-cell lung cancer: a review of current randomized clinical trials and an examination of emerging therapies.
Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy.
Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group.
Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer.
The current status of docetaxel for advanced non-small cell lung cancer.
Prevention of growth of human lung carcinoma cells and induction of apoptosis by a novel phenoxazinone, 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one.
A phase II trial of the cyclin-dependent kinase inhibitor flavopiridol in patients with previously untreated stage IV non-small cell lung cancer.
Synchronous chemoradiation for squamous carcinomas. This treatment is not gold standard for lung cancer.
Flexible chemotherapy regimen with gemcitabine and vinorelbine for metastatic nonsmall cell lung carcinoma: a phase II multicenter trial.
Single-agent mitomycin for advanced non-small cell lung cancer.
Dose escalation study of irinotecan combined with carboplatin for advanced non-small-cell lung cancer.
Interactions of gemcitabine, carboplatin and paclitaxel in molecularly defined non-small-cell lung cancer cell lines.

CancerMail from the National Cancer Institute

1
UI - 21227796
AU - Tognoni A; Pensa F; Vaira F; Vigani A; Bancalari L; Fiasella L; Maggiani R; Canessa P; Pronzato P
TI - A three-drug regimen (gemcitabine, ifosfamide and cisplatin) for advanced non-small-cell lung cancer.
SO - J Chemother 2001 Apr;13(2):202-5
AD - Dept of Medical Oncology, S. Andrea Hospital, La Spezia, Italy.
We have carried out a pilot study on 25 non-small cell lung cancer patients, administering the combination of gemcitabine at the dose of 1000 mg/m2 on days 1 and 8, ifosfamide 1500 mg/m2 on days 1 and 2 (plus mesna as uroprotector) and cisplatin 40 mg/m2 on days 1 and 2, every 21 days. Granulocyte Colony Stimulating Factor was employed in all cases from day 10 to day 18 at the dose of 300 microg daily. An objective response was observed in 11 cases (44%). The regimen was active, but toxicity was remarkable with some cases of severe myelosuppression and mucositis.

2
UI - 21401135
AU - Parente B; Barroso A; Conde S; Guimaraes T; Seada J
TI - A prospective study of gemcitabine and carboplatin as first-line therapy in advanced non-small cell lung cancer: toxicity of a three- versus a four-week schedule.
SO - Semin Oncol 2001 Jun;28(3 Suppl 10):10-4
AD - Department of Pneumology, Centro Hospitalar de Vila Nova de Gaia, Portugal.
We evaluated the toxicity and activity of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) and carboplatin on a 3-week (trial A) versus a 4-week (trial B) schedule in patients with advanced/metastatic non-small cell lung cancer. Chemotherapy-naive patients in trial A received gemcitabine 1,000 mg/m(2) on days 1 and 8 plus carboplatin area under the curve of 5 on day 1, every 3 weeks. In trial B, patients received gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 and carboplatin area under the curve of 6 on day 1, every 4 weeks. Thirty patients were enrolled in trial A and 28 in trial B. Patients received a total of 142 cycles in trial A and 134 in trial B. Despite more frequent treatment delays (82 cycles in trial B and 20 cycles in trial A), and dose reductions/omissions (mainly on day 15), gemcitabine mean dose intensities of both schedules were similar. The principal dose-limiting toxicity was grade 3/4 thrombocytopenia. Objective response rates were 40% in trial A and 68% in trial B (no complete response). Gemcitabine and carboplatin administered on days 1 and 8 every 3 weeks is associated with lower myelotoxicity than that of a 4-week schedule, although both schedules were active against non-small cell lung cancer. Semin Oncol 28 (suppl 10):10-14. Copyright 2001 by W.B. Saunders Company.

3
UI - 21401136
AU - Steele JP
TI - Gemcitabine/carboplatin versus cisplatin/etoposide for patients with poor-prognosis small cell lung cancer: a phase III randomized trial with quality-of-life evaluation.
SO - Semin Oncol 2001 Jun;28(3 Suppl 10):15-8
AD - Department of Medical Oncology, St Bartholomew's Hospital, London, EC1A 7BE, UK.
Small cell lung cancer is a chemosensitive disease; however, patients with extensive-stage disease or adverse prognostic factors are rarely cured. Gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN), a new agent with good tolerability, interacts synergistically with platinum agents. Carboplatin is as effective as cisplatin, but is less toxic. The London Lung Cancer Group is conducting a multicenter, open-label, randomized, phase III trial in patients with histologically or cytologically proven small cell lung cancer and extensive-stage, limited-stage but locally-advanced, or limited-stage disease with poor prognostic factors. Chemotherapy consists of 21-day cycles of gemcitabine 1,200 mg/m(2) intravenous (IV) on days 1 and 8, plus carboplatin area under the curve of 5 IV on day 1, or cisplatin 60 mg/m(2) IV on day 1 plus etoposide 120 mg/m(2) IV on day 1 and 100 mg orally on days 2 and 3. Thirty-nine patients have been randomized to gemcitabine/carboplatin and 38 to cisplatin/etoposide (23 and 22 completed treatment, with 96 and 84 cycles, respectively). Preliminary toxicity data indicate hematologic toxicity in 25% of cycles for gemcitabine/carboplatin and 16% for cisplatin/etoposide, although cisplatin/etoposide-treated patients experienced significant alopecia, nephrotoxicity, nausea and vomiting, and neutropenia. This London Lung Cancer Group trial of gemcitabine/carboplatin may define an active, safe, and acceptable treatment for patients with extensive-stage and poor-prognosis small cell lung cancer. Semin Oncol 28 (suppl 10):15-18. Copyright 2001 by W.B. Saunders Company.

4
UI - 21401134
AU - Domine M; Casado V; Estevez LG; Leon A; Martin JI; Castillo M; Rubio G; Lobo F
TI - Gemcitabine and carboplatin for patients with advanced non-small cell lung cancer.
SO - Semin Oncol 2001 Jun;28(3 Suppl 10):4-9
AD - Servicio de Oncologia, Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Av Reyes Catolicos 2, 28040 Madrid, Spain.
The survival of patients with advanced non-small cell lung cancer remains poor. Cisplatin-based chemotherapy produces a modest benefit in survival compared with that observed with best supportive care. Gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN), a novel nucleoside antimetabolite, is active and well tolerated. The combination of gemcitabine/cisplatin has shown a significant improvement in response rate and survival over cisplatin alone. Phase III trials comparing gemcitabine/cisplatin with older combinations such as cisplatin/etoposide or mitomycin/ifosfamide/cisplatin have shown a higher activity for gemcitabine/cisplatin; however, the best way to combine these drugs remains unclear. In addition, the 3-week schedule has obtained a higher dose intensity with less toxicity and similar efficacy as the 4-week schedule. The role of carboplatin in combination with new drugs is still under evaluation. Gemcitabine/carboplatin seems to be a good alternative, with the advantage of ambulatory administration and lower nonhematologic toxicity. The 4-week schedule has produced frequent grade 3/4 neutropenia and thrombocytopenia in some studies. The 3-week schedule, using gemcitabine on days 1 and 8 and carboplatin on day 1, is a convenient and well-tolerated regimen. The toxicity profile is acceptable without serious symptoms. This schedule could be considered a good option as a standard regimen. Semin Oncol 28 (suppl 10):4-9. Copyright 2001 by W.B. Saunders Company.

5
UI - 21410090
AU - Inoue A; Saijo N
TI - Recent advances in the chemotherapy of non-small cell lung cancer.
SO - Jpn J Clin Oncol 2001 Jul;31(7):299-304
AD - Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
Chemotherapeutic regimens containing new anticancer agents in combination with cisplatin and carboplatin have been demonstrated to be equivalently active against advanced non-small cell lung cancer. The choice of a chemotherapeutic regimen depends on differences in time to progression, response rate, toxicity profile, cost and symptom relief. Several other strategies, such as three-drug combinations, sequential use of a third drug, weekly administration, etc., have been evaluated to improve the chemotherapeutic effect. The sequencing of the human genome may permit targeting of specific abnormalities related to each lung cancer with target-based drugs. This should increase the possibility of application of individualized therapy and, we would hope, improve survival.

6
UI - 21193594
AU - Kakolyris S; Mavroudis D; Tsavaris N; Souglakos J; Tsiafaki P; Kalbakis K; Agelaki S; Androulakis N; Georgoulias V
TI - Paclitaxel in combination with carboplatin as salvage treatment in refractory small-cell lung cancer (SCLC): a multicenter phase II study.
SO - Ann Oncol 2001 Feb;12(2):193-7
AD - Department of Clinical Oncology, University General Hospital of Heraklion, Crete, Greece.
PURPOSE: The activity and toxicity of paclitaxel plus carboplatin combination in patients with disease progression after initial chemotherapy for small-cell lung cancer (SCLC) was investigated in a multicenter phase II study. PATIENTS AND METHODS: Thirty-two patients (twenty-seven men) with extensive stage refractory SCLC after EP or CAV front-line chemotherapy were treated with paclitaxel 200 mg/m2 on day 1 and carboplatin 6 AUC on day 2 in a four-week schedule. The patients' median age was 60 years and the performance status (WHO) was 0 for 9, 1 for 20 and 2 for 3 patients. All patients were evaluable for toxicity and 29 for response. RESULTS: Complete response was observed in one (3%) and partial response in seven (22%) for an overall response rate of 25% (95% confidence interval (CI): 10%-40%). Seven (22%) patients had stable disease and seventeen (53%) progressive disease. All but one of the responders had been previously treated with EP combination and three of them had failed to respond. The median duration of response and the median TTP were 3 and 5.5 months, respectively. The median overall survival was seven months. Grade 3-4 neutropenia was observed in 12 (37%) patients and in 2 of these it was associated with infection. There were no toxic deaths. Grade 4 anaemia was observed in one (3%) patient and grade 3 thrombocytopenia in three (9.4%). Non-hematologic toxicity was very mild with grade 2-3 asthenia occurring in 10 (25%) patients; asthenia was the reason for treatment discontinuation in 3 patients. CONCLUSIONS: The combination of paclitaxel and carboplatin is a relatively active and well-tolerated regimen as salvage treatment in patients with refractory SCLC.

7
UI - 21363325
AU - Rivera MP
TI - Management of patients with advanced non-small-cell lung cancer.
SO - Curr Opin Pulm Med 2001 Jul;7(4):247-58
AD - Department of Pulmonary and Critical Care Medicine, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina 27599-7020, USA. mprivera@med.unc.edu
Lung cancer is one of the most lethal cancers, causing more deaths of men and women than any other cancer in the United States. Non-small-cell lung cancers account for most the newly diagnosed cases of lung cancer. Many patients with non-small-cell lung cancer present with advanced-stage disease and are not appropriate candidates for combined modality therapy. Although these patients have incurable disease, they have a chance of achieving improved 1-year survival rates and palliation of symptoms with chemotherapy. The performance status of patients with advanced non-small-cell lung cancer is the most important determinant of response to chemotherapy.

8
UI - 21375945
AU - Haura EB
TI - Treatment of advanced non-small-cell lung cancer: a review of current randomized clinical trials and an examination of emerging therapies.
SO - Cancer Control 2001 Jul-Aug;8(4):326-36
AD - Thoracic Oncology Program and Clinical Investigations Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.
BACKGROUND: Lung cancer continues to be the leading cause of cancer-related deaths for Americans. As most patients present with nonsurgically curable disease, major efforts have been made in the treatment of advanced non-small-cell lung cancer (NSCLC) with chemotherapy. Several new agents and new combinations of chemotherapy are available. METHODS: The author reviews randomized clinical trials investigating chemotherapy for advanced NSCLC in chemotherapy-naive patients, in patients who present with relapsed or progressive disease, and in elderly patients. Therapies that incorporate new biological agents to target specific aberrations in lung cancer are discussed. RESULTS: Several clinical trials demonstrate improvement in overall survival as well as quality of life with chemotherapy treatment of advanced NSCLC. Better options are available for patients who have relapsed after first-line chemotherapy, and treatment of elderly patients with chemotherapy has demonstrated benefit in survival and quality of life. New agents that target molecular pathways are being tested in patients with early-stage disease. CONCLUSIONS: Despite progress with newer agents for the treatment of advanced NSCLC, only 14% of patients with the disease are alive at 5 years after initial diagnosis. New therapies are needed.

9
UI - 20271999
AU - Shepherd FA; Dancey J; Ramlau R; Mattson K; Gralla R; O'Rourke M; Levitan N; Gressot L; Vincent M; Burkes R; Coughlin S; Kim Y; Berille J
TI - Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy.
SO - J Clin Oncol 2000 May;18(10):2095-103
AD - University of Toronto, Toronto, and London Regional Cancer Centre, London, Ontario, Canada. fshepherd@torhosp.toronto.on.ca
PURPOSE: To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non-small-cell lung cancer who had previously been treated with platinum-based chemotherapy. Secondary end points included assessment of response (docetaxel arm only), toxicity, and quality of life. PATIENTS AND METHODS: Patients with performance statuses of 0 to 2 and stage IIIB/IV non-small-cell lung cancer with either measurable or evaluable lesions were eligible for entry onto the study if they had undergone one or more platinum-based chemotherapy regimens and if they had adequate hematology and biochemistry parameters. They were excluded if they had symptomatic brain metastases or if they had previously been treated with paclitaxel. Patients were stratified by performance status and best response to cisplatin chemotherapy and were then randomized to treatment with docetaxel 100 mg/m(2) (49 patients) or 75 mg/m(2) (55 patients) or best supportive care. Patients in both arms were assessed every 3 weeks. RESULTS: One hundred four patients (103 of whom were eligible for entry onto the study) were well balanced for prognostic factors. Of 84 patients with measurable lesions, six (7. 1%) achieved partial responses (three patients at each dose level). Time to progression was longer for docetaxel patients than for best supportive care patients (10.6 v 6.7 weeks, respectively; P <.001), as was median survival (7.0 v 4.6 months; log-rank test, P =.047). The difference was more significant for docetaxel 75 mg/m(2) patients, compared with corresponding best supportive care patients (7.5 v 4.6 months; log-rank test, P =.010; 1-year survival, 37% v 11%; chi(2) test, P =.003). Febrile neutropenia occurred in 11 patients treated with docetaxel 100 mg/m(2), three of whom died, and in one patient treated with docetaxel 75 mg/m(2). Grade 3 or 4 nonhematologic toxicity, with the exception of diarrhea, occurred at a similar rate in both the docetaxel and best supportive care groups. CONCLUSION: Treatment with docetaxel is associated with significant prolongation of survival, and at a dose of 75 mg/m(2), the benefits of docetaxel therapy outweigh the risks.

10
UI - 20314652
AU - Fossella FV; DeVore R; Kerr RN; Crawford J; Natale RR; Dunphy F; Kalman L; Miller V; Lee JS; Moore M; Gandara D; Karp D; Vokes E; Kris M; Kim Y; Gamza F; Hammershaimb L
TI - Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group.
SO - J Clin Oncol 2000 Jun;18(12):2354-62
AD - Department of Thoracic/ Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030-4009, USA. fossell@mdanderson.org
PURPOSE: To confirm the promising phase II results of docetaxel monotherapy, this phase III trial was conducted of chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC) who had previously failed platinum-containing chemotherapy. PATIENTS AND METHODS: A total of 373 patients were randomized to receive either docetaxel 100 mg/m(2) (D100) or 75 mg/m(2) (D75) versus a control regimen of vinorelbine or ifosfamide (V/I). The three treatment groups were well-balanced for key patient characteristics. RESULTS: Overall response rates were 10.8% with D100 and 6.7% with D75, each significantly higher than the 0.8% response with V/I (P =.001 and P =.036, respectively). Patients who received docetaxel had a longer time to progression (P =.046, by log-rank test) and a greater progression-free survival at 26 weeks (P =.005, by chi(2) test). Although overall survival was not significantly different between the three groups, the 1-year survival was significantly greater with D75 than with the control treatment (32% v 19%; P =.025, by chi(2) test). Prior exposure to paclitaxel did not decrease the likelihood of response to docetaxel, nor did it impact survival. There was a trend toward greater efficacy in patients whose disease was platinum-resistant rather than platinum-refractory and in patients with performance status of 0 or 1 versus 2. Toxicity was greatest with D100, but the D75 arm was well-tolerated. CONCLUSION: This first randomized trial in this setting demonstrates that D75 every 3 weeks can offer clinically meaningful benefit to patients with advanced NSCLC whose disease has relapsed or progressed after platinum-based chemotherapy.

11
UI - 20469581
AU - Gatzemeier U; von Pawel J; Gottfried M; ten Velde GP; Mattson K; DeMarinis F; Harper P; Salvati F; Robinet G; Lucenti A; Bogaerts J; Gallant G
TI - Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer.
SO - J Clin Oncol 2000 Oct 1;18(19):3390-9
AD - Grosshansdorf Hospital, Grosshansdorf, Germany.
PURPOSE: New effective chemotherapy is needed to improve the outcome of patients with advanced non-small-cell lung cancer (NSCLC). Paclitaxel administered as a single agent or in combination with cisplatin has been shown to be a potentially new useful agent for the treatment of NSCLC. PATIENTS AND METHODS: Between January 1995 and April 1996, 414 patients with stage IIIB or IV NSCLC were randomized to received either a control arm of high-dose cisplatin (100 mg/m(2)) or a combination of paclitaxel (175 mg/m(2), 3-hour infusion) and cisplatin (80 mg/m(2)) every 21 days. RESULTS: Compared with the cisplatin-only arm, there was a 9% improvement (95% confidence interval, 0% to 19%) in overall response rate for the paclitaxel/cisplatin arm (17% v 26%, respectively; P=.028). Median time to progression was 2.7 and 4.1 months in the control and paclitaxel/cisplatin arm, respectively (P=.026). The study, however, failed to show a significant improvement in median survival for the paclitaxel/cisplatin arm (8.6 months in the control arm v 8.1 months in the paclitaxel/cisplatin arm, P=.862). There was more hematotoxicity, peripheral neuropathy, and arthralgia/myalgia on the paclitaxel/cisplatin arm, whereas the high-dose cisplatin arm produced more ototoxicity, nausea, vomiting, and nephrotoxicity. Quality of life (QOL) was similar overall between the two arms. CONCLUSION: This large randomized phase III trial failed to show a significant improvement in survival for the paclitaxel/cisplatin combination compared with high-dose cisplatin in patients with advanced NSCLC. However, the paclitaxel/cisplatin combination did produce a better clinical response, resulting in an increased time to progression while providing a similar QOL.

12
UI - 21239582
AU - Green MR
TI - The current status of docetaxel for advanced non-small cell lung cancer.
SO - Anticancer Drugs 2001 Feb;12 Suppl 1():S11-6
AD - Clinical Oncology, Medical University of South Carolina, 96 Jonathan Lucas Street, 903 CSB, Charleston, SC 29425, USA. greenmrk@musc.edu
Docetaxel is an active single agent in both first- and second-line therapy of patients with advanced non-small cell lung cancer (NSCLC). Randomized trials versus best supportive care have documented an improvement in overall survival for docetaxel therapy in both settings. Docetaxel also produced a significant 1-year survival rate improvement when compared with vinorelbine or ifosfamide as second-line therapy. Docetaxel has been extensively investigated in phase I/II studies in combination with cisplatin, carboplatin, irinotecan and gemcitabine. Substantial activity has been demonstrated. In a randomized phase II trial comparing docetaxel plus cisplatin with docetaxel plus gemcitabine, the efficacy of the two regimens was almost identical (response rates 32 and 34%; 1-year survival rates 42 and 38%). However, the combination of docetaxel with gemcitabine was associated with significantly less grade III/IV neutropenia, diarrhea and nausea/vomiting. Three drug regimens combining docetaxel with, for example, gemcitabine and carboplatin or with ifosfamide and cisplatin, are producing very high response rates in phase II trials. Whether three-drug combinations including docetaxel will result in an improved outcome for patients with advanced NSCLC remains to be determined.

13
UI - 21232940
AU - Abe A; Yamane M; Tomoda A
TI - Prevention of growth of human lung carcinoma cells and induction of apoptosis by a novel phenoxazinone, 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one.
SO - Anticancer Drugs 2001 Apr;12(4):377-82
AD - Department of Biochemistry, Tokyo Medical University, Shinjuku 6-1-1, Shinjuku-ku, Tokyo 160-0022, Japan.
Anti-tumor effects of a novel phenoxazinone, 2-amino-4,4-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one (Phx), which was synthesized by the reaction of 2-amino-5-methylphenol with bovine hemoglobin, were studied in terms of suppression of the proliferation of human lung carcinoma cells and apoptosis induction. When Phx was added to cultures of the human lung carcinoma cell lines A549 (adenocarcinoma) and H226 (squamous carcinoma), it caused the growth inhibition and the death of these cells. Phx also fragmented the DNA of these cells to oligonucleosomal-sized fragments, which is characteristic of the apoptosis, dependent on the dose and exposure time. The cellular death caused by the administration of Phx was partially reversed by the addition of Z-VAD-fmk, a caspase family inhibitor. Present results suggest that Phx demonstrates anti-cancer activity against human lung carcinoma cell lines A549 and H226, by inhibiting growth and inducing apoptosis.

14
UI - 21303179
AU - Shapiro GI; Supko JG; Patterson A; Lynch C; Lucca J; Zacarola PF; Muzikansky A; Wright JJ; Lynch TJ Jr; Rollins BJ
TI - A phase II trial of the cyclin-dependent kinase inhibitor flavopiridol in patients with previously untreated stage IV non-small cell lung cancer.
SO - Clin Cancer Res 2001 Jun;7(6):1590-9
AD - Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. geoffrey_shapiro@dfci.harvard.edu
PURPOSE: Flavopiridol is a potent cyclin-dependent kinase inhibitor with preclinical activity against non-small cell lung cancer (NSCLC), inhibiting tumor growth in vitro and in vivo by cytostatic and cytotoxic mechanisms. A Phase II trial was conducted to determine the activity and toxicity of flavopiridol in untreated patients with metastatic NSCLC. EXPERIMENTAL DESIGN: A total of 20 patients were treated with a 72-h continuous infusion of flavopiridol every 14 days at a dose of 50 mg/m(2)/day and a concentration of 0.1-0.2 mg/ml. Dose escalation to 60 mg/m(2)/day was permitted if no significant toxicity occurred. Response was initially assessed after every two infusions; patients treated longer than 8 weeks were then assessed after every four infusions. Plasma levels of flavopiridol were measured daily during the first two infusions to determine steady-state concentrations. RESULTS: This study was designed to evaluate a total of 45 patients in two stages. However, because no objective responses were seen in the first 20 patients, the early-stopping rule was invoked, and patient accrual was halted. In four patients who received eight infusions, progression was documented at 15, 20, 40, and 65 weeks, respectively. The most common toxicities included grade 1 or 2 diarrhea in 11 patients, asthenia in 10 patients, and venous thromboses in 7 patients. The mean +/- SD steady-state concentration of drug during the first infusion was 200 +/- 89.9 nM, sufficient for cytostatic effects in in vitro models. CONCLUSIONS: At the current doses and schedule, flavopiridol does not have cytotoxic activity in NSCLC, although protracted periods of disease stability were observed with an acceptable degree of toxicity.

15
UI - 21432359
AU - Macbeth F; Saunders M
TI - Synchronous chemoradiation for squamous carcinomas. This treatment is not gold standard for lung cancer.
SO - BMJ 2001 Aug 25;323(7310):453

16
UI - 21433642
AU - Hirsh V; Langleben A; Ayoub J; Cormier Y; Pintos J; Iglesias JL
TI - Flexible chemotherapy regimen with gemcitabine and vinorelbine for metastatic nonsmall cell lung carcinoma: a phase II multicenter trial.
SO - Cancer 2001 Aug 15;92(4):830-5
AD - Division of Medical Oncology, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, Quebec H3A 1A1, Canada.
BACKGROUND: This Phase II study evaluated a flexible 3- or 4-week dosing schedule of gemcitabine and vinorelbine to determine its effect on response rate and survival of patients with metastatic nonsmall cell lung carcinoma (NSCLC). METHODS: Thirty-four response-evaluable patients, 24 with performance status (PS) 0-1 and 10 with a PS of 2, 30 with Stage IV, and 4 with Stage IIIB NSCLC were treated with gemcitabine 1000 mg/m(2) intravenously and vinorelbine 25 mg/m(2) intravenously (first 15 patients) or 30 mg/m(2) intravenously (next 19 patients) on Days 1, 8, and 15 of a 4-week cycle, if on Day 15 neutrophils were > or = 1500/uL and platelets > or = 100,000/uL. If chemotherapy could not be administered on Day 15, then Day 22 became Day 1 of the next cycle. RESULTS: When vinorelbine 25 mg/m(2) was given with gemcitabine 1000 mg/m(2), 11 patients received 4-week cycles, 3 patients 3-week cycles, and 1 patient both 3- and 4-week cycles. With vinorelbine 30 mg/m(2) and gemcitabine 1000 mg/m(2), 7 patients received 4-week cycles, 2 patients 3-week cycles, and 10 patients both 3- and 4-week cycles. The partial response rate for 34 patients was 53% (18 patients). Median survival (MS) was 11.1 months, and 1-year survival 50% (17 patients). Patients with PS 0+1 had a MS of 17.5 months compared with patients with PS 2, who had MS of 3.3 months. Patients < 70 years of age had a MS of 18 months, and those >/= 70 years had a MS of 5.5 months. CONCLUSION: This flexible schedule with gemcitabine and vinorelbine enabled optimal dose delivery and suggested excellent efficacy but less toxicity than treatment with platinum regimens. Copyright 2001 American Cancer Society.

17
UI - 21268244
AU - Snee M
TI - Single-agent mitomycin for advanced non-small cell lung cancer.
SO - Clin Oncol (R Coll Radiol) 2001;13(2):99-102
AD - Mid Kent Oncology Centre, Maidstone General Hospital, Maidstone, UK.
In the treatment of patients with advanced non-small cell lung cancer with chemotherapy, there is no consensus concerning the optimum regimen. Survival is poor and the activity of drugs has to be balanced against toxicity. There is therefore continued interest in the use of single-agent chemotherapy for this condition. I report the treatment of non-small cell lung cancer with mitomycin. In 20 patients, four responses were observed, giving a response rate of 20% (95% confidence interval (CI) 3-37); median survival was 26 weeks (95% CI 13-30). One patient who presented with bone and liver metastases survived for 27 months after treatment.

18
UI - 21445679
AU - Takeda K; Negoro S; Takifuji N; Nitta T; Yoshimura N; Terakawa K; Fukuoka M
TI - Dose escalation study of irinotecan combined with carboplatin for advanced non-small-cell lung cancer.
SO - Cancer Chemother Pharmacol 2001 Aug;48(2):104-8
AD - Department of Pulmonary Medicine, Osaka City General Hospital, Japan. kkk-take@ga2.so-net.ne.jp
From December 1994 to July 1997, we conducted a dose escalation study of irinotecan combined with carboplatin in 17 patients with advanced non-small-cell lung cancer (NSCLC) to determine the maximum tolerated dose and the dose-limiting toxicities. Irinotecan was administered intravenously over 90 min on days 1, 8 and 15, with carboplatin given at an area under the concentration-time curve dose of 5 mg/ml x min (calculated using Calvert's formula) on day 1. The starting dose of irinotecan was 30 mg/m2 and dose escalation was done in 10-mg/m2 increments. Treatment was repeated at 28-day intervals for at least two cycles. The dose-limiting toxicities were neutropenia and thrombocytopenia, since three out of five patients given 60 mg/m2 of irinotecan developed grade 4 neutropenia and thrombocytopenia. The overall response rate was 35.3%. The median survival time and the 1-year survival rate were 10.5 months and 35.3%, respectively. The maximum tolerated dose of irinotecan with this regimen was 60 mg/m2, while 50 mg/m2 can be recommended for future use. Further studies of this combination in advanced NSCLC are warranted.

19
UI - 21445684
AU - Edelman MJ; Quam H; Mullins B
TI - Interactions of gemcitabine, carboplatin and paclitaxel in molecularly defined non-small-cell lung cancer cell lines.
SO - Cancer Chemother Pharmacol 2001 Aug;48(2):141-4
AD - University of Maryland Greenebaum Cancer Center, Baltimore 21201-1595, USA. medelman@umm.edu
PURPOSE: To evaluate in vitro interactions of carboplatin, gemcitabine and paclitaxel in molecularly defined non-small-cell lung cancer lines. MATERIALS AND METHODS: Three NSCLC lines, A549 (p16-,p53 wt, Rb wt), Calu-1 (p16-, p53-, Rb+) and H596 (p16 wt, p53 mut, Rb-) were utilized. Cells were exposed to carboplatin, gemcitabine and paclitaxel as individual drugs and in two- and three-drug combinations with various sequences of administration. Cytotoxicity was assessed with the MTT assay. Interactions between the drugs (additive, synergistic and antagonistic) were evaluated by median effect analysis. RESULTS: Gemcitabine and carboplatin were synergistic in all three cell lines. In the A549 line, this synergy was most pronounced when gemcitabine preceded carboplatin. For three-drug combinations, paclitaxel was synergistic with gemcitabine and carboplatin regardless of sequence of administration. CONCLUSIONS: In vitro modeling of gemcitabine and carboplatin as well as gemcitabine/carboplatin and paclitaxel demonstrates synergistic interaction regardless of p16, p53, or Rb status.